The regional cerebral metabolic rate for glucose (rCMRglc) was examined, as a measure of cerebral functional activity in 40 healthy men between the ages of 21 and 83 years. rCMRglc was determined by means of positron emission tomography (PET) with 18-F-2-fluoro-deoxy-D-glucose, under resting conditions, when the subject's eyes were covered and his ears plugged to reduce sensory input. Average hemispheric glucose utilization and glucose utilization in individual regions of the right and left hemispheres did not decline significantly with age (p greater more than 0.05). In young adult subjects with Down syndrome (19-27 yr.), rCMRglc was elevated by 20-40% as compared with age-matched healthy controls, indicating that brains of young adult Down syndrome subjects use glucose excessively despite retardation. In older adults with Down syndrome (greater than 35 yr.), rCMRglc was reduced as compared to its value in younger patients, associated with a decline in cognitive function suggestive of dementia. Similarly, adult patients with autism, an irreversible psychiatric disorder with onset in infancy and with a suspected neurological basis, showed elevated values of rCMRglc, to values between those in normal and Down syndrome subjects, but no change in the pattern of brain metabolism. Adult patients with Alzheimer's disease showed variable reductions in rCMRglc, depending on the cognitive deficits. In mild-moderate Alzheimer's disease, relative rCMRglc was reduced in the parietal lobe as compared to other lobes. In severe Alzheimer's disease, rCMRglc was reduced throughout the cerebral hemispheres. The reductions were correlated with cognitive deficits, as determined by neuropsychological testing.